The objective of this study is to further develop previous work done on this project on reaction to injury in the kidney by focusing specifically on the pathophysiology of acute renal failure using an ischemic and a toxic model. The focus of the research is on the pathophysiology of reversible and irreversible cellular changes in the proximal convoluted tubule which we believe to be the key to the initiation phase of acute renal failure and on the subsequent interactions involving the juxtaglomerular apparatus. The problem will be approached correlating structure, function and biochemical information and an important facet of the strategy is to extend results developed on whole kidney in vivo models of ischemia and toxic acute renal failure to single nephron models and, finally, to isolated single proximal tubular cells. Because of the heterogeneous nature of the kidney cortex and difficulties in interpreting biochemical data, this is of great importance.